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21.
The interaction of the anticancer antibiotic altromycin B and its isostructrural Pt(II) and Pd(II) metal complexes with native calf thymus (CT) DNA was studied using UV-thermal denaturation experiments, circular dichroism spectroscopy and temperature controlled spectrophotometric titrations. Altromycin B stabilizes the double helix by raising the T(m), mainly by intercalation of its chromophore between the base pairs and interacting electrostatically via its sugar moieties with the edges of the DNA helix. Moreover, altromycin B induces a B-->A structural transition of CT DNA. The effect on DNA stability and conformation depends on the metal ion. Pt(II) and Pd(II) complexes induce the B-->A structural transition and stabilize the double helix similarly but they present lower final hyperchromicity due to premelting effects which were caused by intra- and interstrand crosslinking. Thus, a synergic effect of the metal ions to altromycin B-CT DNA interaction is observed in both cases. Altromycin B interacts with 5'-GMP, 5'-AMP and 5'-CMP by electrophilic attack of the opened epoxide ring to the N(7)G, N(1)/N(7)A and N(3)C. Thus, covalent binding between these nucleotides and altromycin B takes place and explain the multiple binding mode suggested by the studies of the interaction of altromycin B and its complexes with DNA. The [Pd(II)-altroB] complex dissociates in the presence of the nucleotides, and various species of Pd(II)-nucleotide complexes, especially with 5'-GMP, are formed. The [Pt(II)-altroB] complex dissociates too, but only one or two species of Pt(II)-nucleotide complexes are formed, and in the case of 5'-AMP interaction the formation of a tertiary altroB-Pt(II)-5'AMP complex is proposed. 5'-TMP reacts very weakly in comparison with the other three nucleotides. These interactions were followed by 1H-NMR. 相似文献
22.
Pantos C Malliopoulou V Paizis I Moraitis P Mourouzis I Tzeis S Karamanoli E Cokkinos DD Carageorgiou H Varonos D Cokkinos DV 《Molecular and cellular biochemistry》2003,242(1-2):173-180
It has been recently shown that long-term thyroxine administration increases the tolerance of the heart to ischaemia. The present study investigated whether thyroxine induced cardioprotection involves alterations in the pattern of p38 mitogen activated protein kinase (p38MAPK) and c-Jun NH2-terminal kinases (JNKs) activation during ischaemia-reperfusion. L-thyroxine (T4) was administered in Wistar rats (25 g/100 g/day, subcutaneously) for 2 weeks (THYR), while normal animals served as controls (NORM). NORM and THYR isolated rat hearts were perfused in Langendorff mode and subjected to 10 or 20 min of zero-flow global ischaemia only and also to 20 min of ischaemia followed by 10, 20 or 45 min of reperfusion. Postischaemic recovery of left ventricular developed pressure at 45 min of reperfusion was expressed as % of the initial value. Activation of p38 MAPK and JNKs was assessed at the different times of the experimental setting by standard Western blotting techniques using a dual phospho p38MAPK and phospho JNKs (p46/p54) antibodies. Activation of p38 MAPK was significantly attenuated during ischaemia and reperfusion in thyroxine treated hearts compared to normal hearts. JNKs were found to be activated only during the reperfusion period. The levels of phospho JNKs were found to be lower in thyroxine treated hearts as compared to untreated hearts, though not at a statistically significant level. Postischaemic functional recovery was higher in THYR as compared to NORM, p < 0.05. In summary, in hearts pretreated with thyroxine, p38 MAPK was attenuated during ischaemia and at reperfusion and this was associated with improved postischaemic recovery of function. 相似文献
23.
Christina Michailidi Stamatios Theocharis Gerasimos Tsourouflis Vasiliki Pletsa Gregorios Kouraklis Efstratios Patsouris Athanasios G Papavassiliou Constantinos Troungos 《Experimental biology and medicine (Maywood, N.J.)》2015,240(12):1599-1605
Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. CRC development is the result of genetic and epigenetic alterations accumulation in the epithelial cells of colon mucosa. In the present study, DNA methylation, an epigenetic event, was evaluated in tumoral and matching normal epithelium in a cohort of 61 CRC patients. The results confirmed and expanded knowledge for the tumor suppressor genes hMLH1, MGMT, APC, and CDH1. Promoter methylation was observed for all the examined genes in different percentage. A total of 71% and 10% of the examined cases were found to be methylated in two or more and in all genes, respectively. mRNA and protein levels were also evaluated. Promoter methylation of hMLH1, MGMT, APC, and CDH1 genes was present at the early stages of tumor’s formation and it could also be detected in the normal mucosa. Correlations of the methylated genes with patient’s age and tumor’s clinicopathological characteristics were also observed. Our findings suggest that DNA methylation is a useful marker for tumor progression monitoring and that promoter methylation in certain genes is associated with more advanced tumor stage, poor differentiation, and metastasis. 相似文献
24.
Rebecca A. Drummond Amanda L. Collar Muthulekha Swamydas Carlos A. Rodriguez Jean K. Lim Laura M. Mendez Danielle L. Fink Amy P. Hsu Bing Zhai Hatice Karauzum Constantinos M. Mikelis Stacey R. Rose Elise M. N. Ferre Lynne Yockey Kimberly Lemberg Hye Sun Kuehn Sergio D. Rosenzweig Xin Lin Prashant Chittiboina Sandip K. Datta Thomas H. Belhorn Eric T. Weimer Michelle L. Hernandez Tobias M. Hohl Douglas B. Kuhns Michail S. Lionakis 《PLoS pathogens》2015,11(12)
Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9
-/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9
-/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. 相似文献
25.
Sideratou Z Kontoyianni C Drossopoulou GI Paleos CM 《Bioorganic & medicinal chemistry letters》2010,20(22):6513-6517
Based on fourth generation diaminobutane poly(propylene imine) dendrimer, a novel targeted drug nanocarrier was prepared, bearing protective PEG chains and a folate targeting ligand. As a control a PEGylated derivative without folate was also synthesized. The encapsulation and release properties of these PEGylated derivatives were investigated employing etoposide, an anticancer hydrophobic drug. Enhanced solubility of etoposide was achieved inside the dendrimeric scaffold which was subsequently released in a controlled manner. These properties coupled with specificity towards the folate receptor and the low toxicity render folate functionalized PEGylated poly(propylene imine) dendrimer promising candidate for targeted drug delivery. 相似文献
26.
Zili Sideratou Dimitris Tsiourvas Theodossis Theodossiou Michael Fardis Constantinos M. Paleos 《Bioorganic & medicinal chemistry letters》2010,20(14):4177-4181
Based on a commercially available hyperbranched aliphatic polyester, novel multifunctional gadolinium complexes were prepared bearing protective PEG chains, a folate targeting ligand and EDTA or DTPA chelate moieties. Their relatively high water relaxivity values coupled with biodegradability of the hyperbranched scaffold, folate receptor specificity render these non-toxic dendritic polymers promising candidates for MRI applications. 相似文献
27.
Tsapatsoulis N Rapantzikos K Pattichis C 《International journal of neural systems》2007,17(4):289-304
In this paper we propose a novel saliency-based computational model for visual attention. This model processes both top-down (goal directed) and bottom-up information. Processing in the top-down channel creates the so called skin conspicuity map and emulates the visual search for human faces performed by humans. This is clearly a goal directed task but is generic enough to be context independent. Processing in the bottom-up information channel follows the principles set by Itti et al. but it deviates from them by computing the orientation, intensity and color conspicuity maps within a unified multi-resolution framework based on wavelet subband analysis. In particular, we apply a wavelet based approach for efficient computation of the topographic feature maps. Given that wavelets and multiresolution theory are naturally connected the usage of wavelet decomposition for mimicking the center surround process in humans is an obvious choice. However, our implementation goes further. We utilize the wavelet decomposition for inline computation of the features (such as orientation angles) that are used to create the topographic feature maps. The bottom-up topographic feature maps and the top-down skin conspicuity map are then combined through a sigmoid function to produce the final saliency map. A prototype of the proposed model was realized through the TMDSDMK642-0E DSP platform as an embedded system allowing real-time operation. For evaluation purposes, in terms of perceived visual quality and video compression improvement, a ROI-based video compression setup was followed. Extended experiments concerning both MPEG-1 as well as low bit-rate MPEG-4 video encoding were conducted showing significant improvement in video compression efficiency without perceived deterioration in visual quality. 相似文献
28.
Giamas G Hirner H Shoshiashvili L Grothey A Gessert S Kühl M Henne-Bruns D Vorgias CE Knippschild U 《The Biochemical journal》2007,406(3):389-398
The involvement of CK1 (casein kinase 1) delta in the regulation of multiple cellular processes implies a tight regulation of its activity on many different levels. At the protein level, reversible phosphorylation plays an important role in modulating the activity of CK1delta. In the present study, we show that PKA (cAMP-dependent protein kinase), Akt (protein kinase B), CLK2 (CDC-like kinase 2) and PKC (protein kinase C) alpha all phosphorylate CK1delta. PKA was identified as the major cellular CK1deltaCK (CK1delta C-terminal-targeted protein kinase) for the phosphorylation of CK1delta in vitro and in vivo. This was implied by the following evidence: PKA was detectable in the CK1deltaCK peak fraction of fractionated MiaPaCa-2 cell extracts, PKA shared nearly identical kinetic properties with those of CK1deltaCK, and both PKA and CK1deltaCK phosphorylated CK1delta at Ser370 in vitro. Furthermore, phosphorylation of CK1delta by PKA decreased substrate phosphorylation of CK1delta in vitro. Mutation of Ser370 to alanine increased the phosphorylation affinity of CK1delta for beta-casein and the GST (gluthatione S-transferase)-p53 1-64 fusion protein in vitro and enhanced the formation of an ectopic dorsal axis during Xenopus laevis development. Anchoring of PKA and CK1delta to centrosomes was mediated by AKAP (A-kinase-anchoring protein) 450. Interestingly, pre-incubation of MiaPaCa-2 cells with the synthetic peptide St-Ht31, which prevents binding between AKAP450 and the regulatory subunit RII of PKA, resulted in a 6-fold increase in the activity of CK1delta. In summary, we conclude that PKA phosphorylates CK1delta, predominantly at Ser370 in vitro and in vivo, and that site-specific phosphorylation of CK1delta by PKA plays an important role in modulating CK1delta-dependent processes. 相似文献
29.
30.
Petrovas C Mueller YM Yang G Altork SR Jacobson JM Pitsakis PG Mounzer KC Altman JD Katsikis PD 《Apoptosis : an international journal on programmed cell death》2007,12(12):2175-2186
We have recently provided data suggesting a potential role for mitochondria and Bcl-2-family molecules in apoptosis sensitivity
of HIV-specific CD8+ T cells. Here, we report on the role of filamentous (F) actin in this process. Disruption of actin by cytochalasin D (cytD)
or lantrunculin A remarkably reduced CD95/Fas-induced apoptosis of HIV-specific CD8+ T cells while their spontaneous apoptosis was unaffected. This inhibition cannot be attributed to changes of CD95/Fas distribution
or levels in these cells. Furthermore, cytD treatment reduced CD95/Fas-induced apoptosis of CD8+ T cells from HIV+ patients independently of their differentiation status. CD95/Fas-induced apoptosis of both CD38+ and CD38− HIV-specific CD8+ T cells was inhibited by cytD treatment indicating that actin mediates this apoptotic process independently of the activation
level of these cells. CytD was found to reduce the activation of caspase-8 induced by short treatment of purified CD8+ T cells from HIV+ patients with anti-CD95/Fas. Our data reveal actin as a critical mediator of HIV-specific CD8+ T cell apoptosis; further analysis of the molecular mechanisms governing this process may potentially contribute to design
new therapies targeting the enhancement of the immune system in HIV infection. 相似文献